Effects of insulin and glucocorticoids on the leptin system are mediated through free leptin

Clin Endocrinol (Oxf). 2001 Apr;54(4):533-9. doi: 10.1046/j.1365-2265.2001.01243.x.


Objective: Insulin and glucocorticoids are known to increase total leptin levels. However, the effects of insulin and glucocorticoids on the components of the leptin system - free leptin (FL), bound leptin (BL) and soluble leptin receptor (SR) - have not been elucidated. The aim of this study was to determine if there is a differential effect of insulin and glucocorticoids on the leptin system.

Material and methods: In the first of two studies (study 1), we measured free leptin (FL), bound leptin (BL), a soluble leptin receptor (SR) and insulin, by specific RIA methods, in six healthy subjects on a control day, and subsequently during a hyperinsulinaemic euglycaemic clamp study. In the second study (study 2) we measured the same parameters in six healthy subjects, before (day 1) and during administration of dexamethasone over 3 consecutive days.

Results: In study 1, on the control day FL levels rose over the 16 h monitoring period (P = 0.057) and SR levels declined (P < 0.001), but there was no change of BL levels. Even after accounting for diurnal variation, FL levels increased even more substantially over 12 h of insulin infusion than observed on the control day (P < 0.001). In study 2, mean FL concentration doubled from day 1 to day 2 (P = 0.01) and remained elevated subsequently. In contrast to FL, BL and SR levels remained unchanged during the study. Fasting insulin levels (pmol/l) increased from day 1 to day 2, but this rise only approached significance on day 4 (P = 0.05).

Conclusion: We conclude that insulin and dexamethasone increase free leptin levels, but do not change the concentrations of bound leptin and soluble leptin receptor. Furthermore, the dexamethasone-induced rise in leptin levels is (at least partially) independent of the effects of glucocorticoid-induced hyperinsulinaemia.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Carrier Proteins / blood*
  • Circadian Rhythm
  • Dexamethasone*
  • Female
  • Glucocorticoids*
  • Humans
  • Insulin* / blood
  • Leptin / blood*
  • Linear Models
  • Male
  • Radioimmunoassay / methods
  • Receptors, Cell Surface*
  • Receptors, Leptin


  • Carrier Proteins
  • Glucocorticoids
  • Insulin
  • Leptin
  • Receptors, Cell Surface
  • Receptors, Leptin
  • leptin receptor, human
  • Dexamethasone